The proposed program will develop a novel near-infrared laser based spectrophotometer suitable for transcutaneous determination of blood glucose. Non-invasive blood glucose monitors that utilize conventional spectrometers and thermal light sources suffer from insufficient signal-to-noise ratio for the stable prediction of glucose concentration. The laser-based system we propose to develop and test is expected to exhibit superior signal-to-noise measurements of glucose, and therefore better sensitivity and specificity. These in turn will provide a better account for physiological and phenotypic variables. The proposed technology has the significant advantage over other approaches of being based upon an inherently miniaturizable, power-efficient, and mechanically stable technology that will permit the development of a compact robust system. This technology promises to produce a fundamental improvement in the frequency with which diabetic patients monitor their blood glucose. It will have a major impact on the public health issues arising from diabetes. Phase I of this project will determine the feasibility of the proposed approach by in-vitro measurements of clinical samples of whole blood. During Phase II of this project a prototype of a hand-held in-vivo monitor based upon the system engineered in Phase I will be constructed, and clinical trials will be conducted. Total diabetes glucose self-monitoring devices market for the U.S. alone was valued at $1.2 billion. There are number of industries that this technology could provide benefits. Besides obvious applications in medical devices for glucose measurements, and monitoring other metabolites in human body, it can be used in food and pharmaceutical industries, as well as for environmental monitoring and industrial safety.